Coronary heart disease (CHD) is the leading cause of death in the United States, affecting 600,000 Americans each year. The term cardiovascular vulnerable patient has been used to describe patients susceptible to acute coronary events based upon plaque, blood, or myocardial characteristics. Recent evidence has suggested that anxiety, which is common in CHD patients, may be a significant and independent prognostic factor that also increases cardiovascular vulnerability. This evidence has provided a rationale for reducing anxiety in cardiac patients. Anxiolytic medications, especially selective serotonin reuptake inhibitors (SSRIs), may be effective in this regard, although the value of these medications in reducing anxiety has not been widely studied in cardiac patients and their value in improving clinical outcomes is not known. Exercise also may be effective in reducing anxiety, although the therapeutic potential of exercise has remained unfulfilled due to a paucity of data from well-designed clinical studies. The study proposed in this application will (a) evaluate the effectiveness of exercise training and anxiolytic medication in reducing anxiety in vulnerable cardiac patients; (b) examine changes in intermediate endpoints, including measures of autonomic nervous system dysregulation, vascular endothelial dysfunction, and chronic inflammation, which also serve as physiologic markers of vulnerability to adverse cardiac events; (c) follow participants for up to 4 years to assess clinical events including fatal and non fatal cardiac events, hospitalizations, and medical costs; and (d) explore possible mechanisms by which the interventions improve outcomes. One hundred fifty men and women with CHD and an anxiety disorder or elevated symptoms of anxiety will be randomly assigned to Exercise, Medication (escitalopram), or Placebo. Before and after 3 months of treatment, patients will undergo clinical assessments of anxiety and measures of autonomic nervous system regulation, vascular endothelial function, and inflammation. A six month follow-up will assess maintenance of psychological benefit and clinical outcomes will be monitored for up to 4 years. The data generated from this study will have important clinical significance by determining the extent to which exercise and medication may reduce anxiety, improve intermediate markers of CHD risk, and improve medical outcomes including clinical events and CHD-related hospitalizations.